NK3

▎药明康德内容团队编辑今日，知名商业媒体《快公司》（Fast Company）公布了“全球最具创新力的10家医药公司名单”。这份名单反映了过往一年治疗顽固性疾病上的重大突破，许多上榜公司为以往难以有效治疗的疾病带来“首款”或“改变游戏规则”的疗法，这些领域包含阿尔茨海默病、血友病、抑郁症等。这些入选公司代表着人类在医药创新路程中的前锋，其所开发的创新科技也代表着未来产业界的潜在方向。图片来源：123RF诺和诺德：释放GLP-1疗法在糖尿病与减重以外的潜力诺和诺德旗下重磅药物司美格鲁肽（semaglutide）分别在2017年与2021年获美国FDA批准上市，用于2型糖尿病患者的血糖控制（商品名：Ozempic）与治疗普通肥胖患者（商品名：Wegovy），该款药物的成功上市推动该公司的整体成长。然而诺和诺德并不止步于此，除了在减重与糖尿病领域持续不断布局外，该公司还积极探索司美格鲁肽在不同疾病的潜在应用，包含用于治疗早期阿尔茨海默病、非肝硬化非酒精性脂肪性肝炎（NASH）/代谢功能障碍相关脂肪性肝炎（MASH），以及降低2型糖尿病和慢性肾病（CKD）患者发生肾病相关事件风险等。这个月，Wegovy再获美国FDA批准，成为获批用于辅助患有心血管疾病及肥胖或超重的成年人预防重大心血管事件的首款减重药物。参考阅读：12周体重下降超13%！诺和诺德下一代减重疗法最新结果与公司开发战略公布Vertex Pharmaceuticals：将首款CRISPR疗法推进上市2023年11月Vertex及其合作伙伴CRISPR Therapeutics共同开发的CRISPR基因编辑疗法Casgevy（exagamglogene autotemcel，exa-cel）在英国获批上市，成为全世界首款获批的CRISPR基因编辑疗法。美国FDA也随后在2023年12月与今年1月先后批准该疗法用于治疗镰刀型细胞贫血病（SCD）与输血依赖性β地中海贫血（TDT）患者。除了专注于基因编辑疗法的开发，Vertex也即将递交其选择性NaV1.8抑制剂VX-548用于治疗中度至重度急性疼痛的新药申请。新闻稿指出，如果获得批准，这将成为数十年来首款具有新作用机制的止痛药。此外，Vertex也在上个月公布其用以治疗囊性纤维化（CF）的新一代三联疗法（vanzacaftor/tezacaftor/deutivacaftor）在三项3期临床试验中获得积极结果，该公司预计在2024年年中向美国、欧盟和加拿大的监管机构递交上市申请。卫材：致力于开发靶向淀粉样蛋白斑块的阿尔茨海默病疗法开发去年1月，由卫材（Eisai）和渤健（Biogen）联合开发的Leqembi（lecanemab）获得美国FDA的加速批准，治疗阿尔茨海默病，成为首款能延缓疾病进程、缓解认知功能衰退的获批疗法。Leqembi并在同年7月进一步获得FDA的完全批准，这是20年来FDA首次完全批准一款阿尔茨海默病药物。这款药物也登上《时代》周刊所发布的2023年度最佳发明的榜单。Leqembi与β淀粉样蛋白的可溶性寡聚体特异性结合。不但可以中和并清除具有毒性的可溶性寡聚体，还能快速降低患者大脑中的淀粉样蛋白沉积。在名为CLARITY AD的3期临床试验中，Leqembi与安慰剂相比，显著降低了试验主要终点CDR-SB的增加速度（CDR-SB评分越高意味着患者临床功能越低）。在第79周时与安慰剂组相比，平均CDR-SB评分的变化降低27%。公司同时也在开发更为方便使用的Leqembi皮下制剂，相关生物制品许可申请（BLA）预计在近日向FDA递交。Sage Therapeutics：开发出更快、更简便的产后抑郁症疗法美国FDA在去年8月批准由Sage Therapeutics和渤健共同开发的Zurzuvae（zuranolone）上市，使其成为首个获批用以治疗产后抑郁症（PPD）成人患者的口服疗法。在此之前，PPD患者的治疗仅可通过医护人员在医疗机构通过静脉注射给药。PPD是妊娠期间和妊娠后最常见的并发症之一。PPD可能给女性带来严重的负面影响，包括严重的功能障碍、情绪低落和/或对新生儿失去兴趣，以及相关的抑郁症状。之前所公布的3期试验结果显示，Zurzuvae达成试验主要终点以及所有的关键次要终点。参与者在使用药物第3天开始便有快速与显著的抑郁症状改善，并一直持续至第45天。Perrigo：推出首款非处方避孕药Perrigo所开发的Opill（norgestrel）片剂在2023年7月获得美国FDA批准，成为首个获批不用处方就可使用的每日口服避孕药。Opill仅含孕激素（progestin）一种有效成分，使用者可在一般药店、便利商店与网上自行购买。在过去，其他经批准的口服避孕药的配方和剂量只能通过医疗人员拿到处方后获得。根据FDA新闻稿，在美国，每年大约有610万例怀孕，其中近一半属于意外怀孕。意外怀孕与不良的孕产结果密切相关，这包括减少获得早期产前护理的机会、增加早产的风险，以及不利于新生儿、儿童发展和健康的后果。使用非处方的Opil可能有助于降低意外怀孕的发生率及其可能带来的负面后果。赛诺菲：保护独特的弱势患者群体在2023年，赛诺菲公司的两款创新疗法获得美国FDA的批准，解决了独特弱势患者群体的未竟医疗需求。2023年2月，赛诺菲的Altuviiio获得美国FDA的批准，这是首款只需每周一次治疗，就可预防血友病A患者出血的疗法。通常血友病A患者需要每周接受3-4次凝血因子VIII输注，这为他们的生活带来极大的不便。在名为XTEND-1的临床试验中，Altuviiio与预防性凝血因子VIII治疗相比，在预防出血方面也表现出优效性，显著降低血友病A患者的年出血率。此外，赛诺菲和阿斯利康联合开发的呼吸道合胞病毒（RSV）抗体Beyfortus（nirsevimab）也在2023年7月获得美国FDA批准上市。Beyfortus是首个只需一剂，就可以为所有婴儿和有感染风险的幼儿提供针对RSV保护的疗法。安斯泰来：开发首款治疗潮热的创新疗法安斯泰来开发的口服药物Veozah（fezolinetant）在2023年5月首次获得美国FDA的批准上市，用于治疗由于更年期引起的中度至重度血管舒缩症状（VMS，即潮热）。Veozah是神经激肽3（NK3）受体拮抗剂，可通过与受体结合以阻断其作用。神经激肽3受体参与大脑调节体温的机制。Veozah不是一种激素，而是靶向引起更年期潮热的神经活动。2023年7月公布的3b期临床试验结果显示，从基线到第24周，与安慰剂组相比，接受45 mg Veozah的患者的中度至重度VMS的发生频率在统计学上显著降低。Blueprint Medicines：为罕见血液疾病提供首款精准疗法2023年5月，Blueprint Medicines公司的Ayvakit（avapritinib）获得美国FDA的批准，治疗惰性系统性肥大细胞增多症（SM）成人患者。它是获批治疗惰性SM的首款精准疗法。Ayvakit是一种靶向激酶激活构象的1型抑制剂，它能够抑制多种携带KIT和PDGFRA基因突变的蛋白激酶。在约95%的SM患者中带有KIT蛋白D816V突变。Ayvakit的批准是基于双盲、安慰剂对照的临床试验PIONEER的数据。在该试验中，惰性SM患者每日一次接受25 mg的Ayvakit治疗并辅以支持性护理，对照组成员则接受安慰剂治疗外加支持性护理。相对于安慰剂治疗，Ayvakit在主要和所有关键次要终点上都显示出了显著的改善，包括总体症状和肥大细胞负荷。安进：扩展自身免疫疾病治疗的可及性2023年10月，安进公司开发的Wezlana获得美国FDA的批准，成为首款可替换重磅药物Stelara的可替换生物类似药（interchangeable biosimilar）。这款药物可治疗斑块状银屑病、银屑病关节炎、克罗恩病和溃疡性结肠炎。Wezlana无需咨询医生就可用于替代Stelara，它的上市有望扩展多种自身免疫疾病治疗的可及性。百济神州：为治疗常见白血病提供新选择2023年，百济神州开发的布鲁顿氏酪氨酸激酶抑制剂Brukinsa（泽布替尼）获得美国FDA的批准，用于治疗慢性淋巴细胞白血病（CLL）或小淋巴细胞淋巴瘤（SLL），这是最常见的白血病类型之一。这个月该款药物再获FDA加速批准，用以治疗既往经过至少二线系统治疗的复发或难治性（R/R）滤泡性淋巴瘤（FL）成人患者。2022年12月在《新英格兰医学杂志》发表的3期临床试验ALPINE的试验结果显示，泽布替尼与活性对照组相比，在无进展生存期（PFS）和总缓解率（ORR）方面均达到优效性标准。24个月时，泽布替尼组研究者评估的无进展生存率为78.4%，活性对照组为65.9%。经独立评审委员会（IRC）评估，在所有主要亚组中均观察到PFS获益，包括携带特定TP53突变的高风险患者亚组。泽布替尼是一款由百济神州科学家自主研发的BTK小分子抑制剂，目前正在全球进行广泛的临床试验项目，作为单药和与其他疗法进行联合用药治疗多种B细胞恶性肿瘤。由于新的BTK会在人体内不断合成，泽布替尼的设计通过优化生物利用度、半衰期和选择性，实现对BTK蛋白完全、持续的抑制。凭借与其他获批BTK抑制剂存在差异化的药代动力学，泽布替尼能在多个疾病相关组织中抑制恶性B细胞增殖。它在2019年首次获得美国FDA批准，迄今为止已获FDA批准5项适应症。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] The most innovative companies in medicines and therapeutics for 2024. Retrieved March 19, 2024 from https://www.fastcompany.com/91037063/medicines-therapeutics-most-innovative-companies-2024[2] FDA Approves First Nonprescription Daily Oral Contraceptive. Retrieved March 19, 2024 from https://www.fda.gov/news-events/press-announcements/fda-approves-first-nonprescription-daily-oral-contraceptive免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

BERLIN--( BUSINESS WIRE )--Bayer today announced positive topline results of the Phase III study OASIS 3 evaluating the efficacy and long-term safety of the investigational compound elinzanetant versus placebo. In this study, elinzanetant successfully met the primary endpoint demonstrating statistically significant reduction in the frequency of moderate to severe vasomotor symptoms (VMS, also known as hot flashes) from baseline to week 12 compared to placebo. The long-term safety profile observed over 52 weeks in the OASIS 3 study is overall consistent with previously conducted studies and published data 1,2 on elinzanetant. “OASIS 3 was designed to address the important question of the long-term profile of elinzanetant. With the positive topline results of OASIS 3 adding to the existing evidence from OASIS 1 and 2, elinzanetant has consistently shown positive data across all Phase III clinical trials in the treatment of moderate to severe VMS associated with menopause,” said Dr. Christian Rommel, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development. “We are looking forward to sharing the full data at upcoming medical conferences as we move towards submitting to health authorities.” Elinzanetant is the first dual neurokinin-1,3 (NK-1,3) receptor antagonist, in late-stage clinical development for the non-hormonal treatment of moderate to severe VMS associated with menopause, administered orally once daily. “It is critical that we continue to broaden therapeutic options that will effectively meet the significant needs of menopausal women,” said Nick Panay, Principal Investigator for OASIS 3, Consultant Gynaecologist, Imperial College Healthcare NHS Trust, Professor of Practice, Imperial College London and President of International Menopause Society. “These results, coupled with the recent announcement of topline data for OASIS 1 and OASIS 2, strengthen our confidence in the proposed efficacy and safety of elinzanetant as a potential novel non-hormonal solution for women experiencing menopause-related symptoms.” OASIS 3 (NCT05030584) is the third Phase III study in the OASIS clinical development program with positive topline results. In early 2024, Bayer announced topline data of the first two Phase III studies OASIS 1 and 2 (NCT05042362 and NCT05099159) which met all primary and key secondary endpoints. The results of all three studies will be presented at upcoming scientific congresses. Bayer will submit the data from the OASIS 1, 2 and 3 studies to health authorities for approval of marketing authorizations of elinzanetant for the treatment of moderate to severe VMS associated with menopause. About the OASIS 1, 2 and 3 studies OASIS 1 and 2 are double-blind, randomized, placebo-controlled multicenter studies investigating the efficacy and safety of elinzanetant administered orally once daily in women with moderate to severe VMS associated with menopause over 26 weeks. OASIS 1 and 2 randomized 396 and 400 postmenopausal women between 40 and 65 years across 184 sites in 15 countries. OASIS 3 is a double-blind, randomized, placebo-controlled multicenter study to investigate the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms over 52 weeks in postmenopausal women. OASIS 3 randomized 628 postmenopausal women between 40 and 65 years across 83 sites in 9 countries. About the OASIS Clinical Development Program The Phase III clinical development program of elinzanetant, OASIS, currently comprises four Phase III studies: OASIS 1, 2, 3 and 4. The OASIS 1, 2 and 3 studies investigate the efficacy and safety of elinzanetant 120 mg in women with moderate to severe VMS associated with menopause. The OASIS 4 study is an expansion of the clinical phase III program and investigates the efficacy and safety of elinzanetant in women with moderate to severe VMS caused by endocrine therapy for treatment or prevention of breast cancer. The design and dosing of the Phase III clinical development program is based on the positive data from two Phase II studies (RELENT-1 and SWITCH-1). RELENT-1 was a Phase Ib/IIa study investigating the safety, pharmacokinetics and preliminary efficacy of elinzanetant. SWITCH-1 was a Phase IIb study investigating the efficacy and safety of four different doses of elinzanetant compared to placebo in women with VMS. About Elinzanetant Elinzanetant is the first dual neurokinin-1,3 (NK-1,3) receptor antagonist, in late-stage clinical development for the non-hormonal treatment of moderate to severe VMS associated with menopause, administered orally once daily. Elinzanetant may address moderate to severe VMS by modulating a group of estrogen sensitive neurons in the hypothalamus region of the brain (the KNDy neurons) which, with the decrease of estrogen, become hypertrophic and lead to a hyperactivation of the thermoregulatory pathway, consequently disrupting body heat control mechanisms resulting in VMS. Elinzanetant may also decrease sleep disturbances associated with menopause. About Vasomotor Symptoms Vasomotor symptoms (VMS; also referred to as hot flashes) result from hyperactivation of the thermoregulatory pathway mediated by hypertrophy of the KNDy neurons. This is due to a decrease of estrogen, which can result from the progressive reduction of ovarian function due to natural menopause or medical intervention by bilateral oophorectomy or endocrine therapy. VMS are reported by up to 80% of women at some point during the menopausal transition and are one of the leading causes for seeking medical attention during this phase of a woman’s life. Over one-third of menopausal women report severe symptoms, which can last 10 years or more after the last menstrual period, with relevant impact on quality of life. VMS may also be caused by endocrine therapy, for the treatment or prevention of breast cancer, impacting quality of life and treatment adherence. For these women, there are currently no approved treatment options. About Menopause By 2030, the world population of women experiencing menopause is projected to increase to 1.2 billion, with 47 million new women entering this phase each year. Menopause is a transitional phase in women’s lives, related to the progressive decline of ovarian function, and which usually occurs in women during their 40s or early 50s. It can also be the result of surgical or medical treatment, for example breast cancer treatment. The hormonal decline can lead to various symptoms which can substantially affect a woman’s health, quality of life, healthcare utilization and work productivity. The most frequently reported and disruptive symptoms during the menopausal transition are VMS, sleep disturbances and mood changes. Addressing these symptoms is key to maintaining functional ability and quality of life in menopause which is highly relevant from both a healthcare and socio-economic perspective. About Women’s Healthcare at Bayer Women’s Health is in Bayer’s DNA and as a global leader in women’s healthcare Bayer has a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. Bayer offers a wide range of effective short- and long-acting birth control methods as well as therapies for menopause management and gynecological diseases. Bayer is also focusing on innovative options to address the unmet medical needs of women worldwide and to broadening treatment choices such as in menopause. Additionally, Bayer intends to provide 100 million women per year in low-and-middle income countries by 2030 with access to family planning by funding multi-stakeholder aid programs for capacity building and by ensuring the supply of affordable modern contraceptives. This is part of the comprehensive sustainability measures and commitments from 2020 onwards and in line with the Sustainable Development Goals of the United Nations. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer Follow us on Twitter: @BayerPharma kw (2024-0048e) Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References: 1 Simon JA, Anderson RA, Ballantyne E, Bolognese J, Caetano C, Joffe H, Kerr M, Panay N, Seitz C, Seymore S, Trower M, Zuurman L, Pawsey S. Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1). Menopause. 2023 Mar 1;30(3):239-246. 2 Trower M, et al. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause: The Journal of The North American Menopause Society. 2020; 27 (5): 498-505.

Bayer reported further positive Phase III study results for elinzanetant in treating severe vasomotor symptoms (VMS) associated with menopause, but the wait continues for detailed data to see how the NK-1,3 receptor antagonist stacks up against Astellas' marketed drug Veozah (fezolinetant).In January, Bayer announced that elinzanetant met the primary endpoints of the OASIS 1 and 2 trials in women with VMS associated with menopause, with the oral drug demonstrating statistically significant reductions in the frequency and severity of moderate-to-severe VMS from baseline to week four and 12 compared to placebo.Meanwhile, the results disclosed Tuesday come from the OASIS 3 study, with elinzanetant again demonstrating a statistically significant reduction in the frequency of moderate-to-severe VMS from baseline to week 12 compared to placebo. Bayer added that the long-term safety profile observed over 52 weeks in the trial was “overall consistent” with previously conducted studies.Results from all three OASIS studies are expected to be presented at upcoming medical meetings, with elinzanetant’s safety profile seen as key to competing with Astellas’ NK3 receptor antagonist. Veozah’s label in the US includes a warning for elevated hepatic transaminase and requires blood tests for liver damage or infection prior to treatment and every three months for the first nine months of use.Bayer said it will submit the data from the OASIS programme to health authorities seeking approval of elinzanetant for the treatment of moderate-to-severe VMS associated with menopause.More to come.